[Livedo reticularis following administration of COVID-19 vaccine: a case report]. / Livédo réticulaire post vaccin anti COVID-19: à propos d'un cas.

The emergence of severe acute respiratory syndrome coronavirus 2 has made it crucial to develop safe vaccines. Three main types of vaccines are currently available. Although they have proven to be very secure, they have caused various adverse effects. We here report a rare case of livedo reticularis following the administration of COVID-19 vaccine in a 54-year-old woman. It occurred 24 hours after vaccination, accompanied by respiratory, digestive, and neurological disorders and deterioration in general condition. Examinations revealed skin lesions compatible with livedo reticularis, mild inflammatory syndrome and hypercholesterolemia. Imaging showed no abnormalities. Immunological tests were positive for lupus anticoagulant. The patient received symptomatic treatment, with improvement in neurological and joint symptoms and a slight regression of skin rashes. After three months, the lupus anticoagulant test remained positive, confirming post-vaccination antiphospholipid syndrome (APS). The association of livedo reticularis with COVID-19 vaccine should not be underestimated and its degree of severity remains to be determined. More data and cases need to be collected for a more in-depth and detailed analysis.

Central retinal artery occlusion as the initial manifestation of mixed connective tissue disease in a young woman: a case report.

BACKGROUND: Retinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman. CASE PRESENTATION: A 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD). CONCLUSION: In young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae.

The Validation of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria in a Cohort from Turkey.

BACKGROUND/OBJECTIVES: Our aim was to validate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for antiphospholipid syndrome (APS), published in 2023, in an APS cohort. METHODS: A total of 193 patients, 83 with APS (secondary APS, n = 45; primary APS, n = 38) and 110 without APS (systemic lupus erythematosus (SLE), n = 100; others, n = 10), were included in this study. The performance (sensitivity, specificity and area under the curve (AUC)) of the 2023 ACR/EULAR classification criteria for APS was evaluated and the agreement with the revised Sapporo criteria was compared using the kappa test. RESULTS: In our cohort, the sensitivity and specificity of the 2023 ACR/EULAR classification criteria for APS were 73% and 94%, respectively (AUC: 0.836, 95% CI: 0.772-0.899), while the sensitivity and specificity of the revised Sapporo criteria were 66% and 98%, respectively (95% CI: 0.756-0.888). The performance of the two sets of criteria in our cohort was significantly consistent and significant (p < 0.001). When the sensitivity, specificity and ROC curve analysis were performed again by excluding livedo racemosa, the sensitivity of the new criteria in our cohort was 62% and the specificity was 100% (AUC: 0.813, 95% CI: 0.746-0.881). CONCLUSIONS: Although the newly published criteria broaden the scope of APS classification by including clinical findings other than thrombosis and obstetric criteria, their sensitivity in our cohort was low. On the other hand, we found that the specificity of the criteria in our cohort reached 100% when livedo findings were excluded.

Dermatological Manifestations of Disseminated Bacillus Calmette-Guerin Infection in the Intensive Care Unit.

We report a case of disseminated Bacillus Calmette-Guerin (BCG)-itis with zosteriform skin eruption, purpura, and livedo racemosa in a 70-year-old critically ill patient who has a history of in situ bladder carcinoma treated with intravesical BCG instillations for the last three years. He presented with fever, fatigue, and a painful lesion on his back, initially diagnosed as herpes zoster. Despite antiviral treatment, he exhibited persistent fever, an inflammatory syndrome, and mild liver enzyme elevation. Initial imaging revealed findings consistent with pneumonia, for which antibiotics were prescribed with no improvement. A subsequent fluorodeoxyglucose (FDG) PET scan identified hypermetabolic lesions in the liver, prompting a biopsy that showed non-caseating granulomas. Skin biopsies from the zosteriform papular eruption on the back and purpura with livedo racemosa on the right foot revealed non-caseating granulomas. Specific Wade Fite staining performed on skin biopsies indicated evidence of mycobacterial infection. Additionally, cultures and Ziehl-Nielsen staining of blood and bone marrow confirmed Mycobacterium bovis infection, establishing the diagnosis of disseminated BCG-itis. Treatment with rifampicin, ethambutol, and moxifloxacin, and a later switch to isoniazid, along with corticosteroids, resolved the skin lesions and improved the patient's condition. This case underscores the diagnostic challenges and the importance of considering disseminated BCG-itis in patients treated with prior intravesical BCG instillations for in situ bladder carcinoma presenting with persistent fever, multi-organ involvement, and diverse skin manifestations including zosteriform papules, purpura, and livedo racemosa.

Combination therapy for Sneddon syndrome to reduce the incidence of cerebrovascular complications.

BACKGROUND: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results. PATIENTS AND METHODS: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. RESULTS: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients. CONCLUSIONS: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome.

Sneddon Syndrome: A Case Report From Saudi Arabia.

Sneddon syndrome, also known as livedo reticularis with cerebrovascular accidents, is a rare but chronic condition that affects blood vessels in the skin and brain. This syndrome is characterized by a net-like appearance on the skin, known as livedo reticularis, which occurs due to the constriction of blood vessels. In addition to skin manifestations, Sneddon syndrome is often associated with repeated neurological events, such as strokes or transient ischemic attacks. These neurological symptoms can vary in severity and can lead to various complications. Upon admission to the stroke unit, a 28-year-old female was found to have bilateral livedo reticularis affecting the soles and the dorsal sides of the hands. Patient evaluation is done through medical history, physical examination, routine laboratory tests, and other diagnostic procedures.

Nicolau Syndrome Following Glatiramer Injection in a Middle-Aged Woman.

Nicolau syndrome is a rare adverse reaction that can occur in the setting of intramuscular, intravenous, and subcutaneous injections. Proper diagnosis and management are critical to avoid complications including abscesses, muscular atrophy, and necrotizing fasciitis. Here, we report a 55-year-old female with multiple sclerosis who presented to our clinic following a subcutaneous injection of 40mg of glatiramer. She immediately noted a sharp pain and erythema, which developed into a purple discoloration, became purulent, and eventually necrosed. The patient's wound was debrided, and she was advised to clean the wound with soap and water, apply topical mupirocin, and change dressings twice daily. She continued to receive appropriate follow-up care with weekly to bi-weekly debridement with excellent resolution.

Painful, Tender, Localized, Idiopathic Livedo Reticularis.

Livedo reticularis (LR) is a unique cutaneous condition characterized by a reddish-blue to purple, net-like cyanosis of the skin, often associated with disturbances in cutaneous blood flow. This case report discusses a 30-year-old woman with a history of Hashimoto thyroiditis, vitamin D deficiency, migraines, and goiter who presents with painful, localized LR on her right flank. Despite her extensive medical history, there were no significant findings in her laboratory and imaging studies, including a normal epidermis in skin biopsies. The LR in this case is distinguished by its persistence and the presence of pain, a symptom not commonly associated with LR. Various treatments, including 5% lidocaine ointment, oral analgesics, and gabapentin, were considered, but her symptoms remained stable over 13 months. This case exemplifies the complexity of LR, particularly when presenting with atypical symptoms like pain. It highlights the need for further research into the pathophysiology and treatment of LR, especially in cases deviating from the typical symptomatology, and suggests the potential value of a multi-disciplinary approach to management.

Adenosine deaminase 2 deficiency in a Chinese patient: Report of one novel mutation and literature review.

OBJECTIVE: Through a case of deficiency of adenosine deaminase 2 (DADA2) to improve domestic clinicians' understanding of the disease, and to review the literature, promote dermatologists for clinical secondary primary lesion diagnosis. METHOD: Analysis of a case diagnosed with DADA2 deficiency of clinical manifestations, laboratory, imaging examination and treatment methods, and discussion through literature analysis. RESULTS: The child with recurrent fever, limbs nodular erythema, gradually in the limbs. CT of lower limb skin showed mild edema of the spinous layer, intact basal layer, dilated vascular congestion in the superficial dermis, visible RBC extravasation, and changes of telangiectasia ring purpura were considered. Cranial magnetic resonance imaging (MRI) showed a left choroidal cleft cyst. Genetic test was the CECR1 mutation. The treatment with adalimumab was effective. CONCLUSION: In this case, DADA2 is the seventh case in China, and the CECR1 mutation site (c.254A> T p.N85I,c.851G>T p. G284V) was a compound heterozygous mutation. Mastering the clinical characteristics is helpful for clinicians to diagnose this disease.

Cutaneous vasculitis in autoinflammatory diseases.

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes.

Sneddon's syndrome concurrent with cerebral venous sinus thrombosis: A case report.

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with Sneddon's syndrome (SS) and cerebral venous sinus thrombosis (CVST). Particular emphasis is placed on the comprehensive elucidation of SS's clinical manifestations, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A 26-year-old woman presented with recurrent episodes of paroxysmal unilateral limb weakness accompanied by skin mottling, seizures, and cognitive impairment. Digital subtraction angiography revealed CVST. Despite negative antiphospholipid antibody results, skin biopsy indicated chronic inflammatory cell infiltration. The patient was treated using anticoagulation, antiepileptic therapy, and supportive care, which resulted in symptom improvement. The coexistence of SS and CVST is rare and the underlying pathophysiology remains uncertain. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of SS with CVST and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Clinical characteristics of Martorell hypertensive ischaemic leg ulcer.

OBJECTIVE: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: 'the red lipstick sign'; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. METHOD: A single-centre, retrospective cohort study was conducted between 2015-2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. RESULTS: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The 'red lipstick-like' margin covered 0-50% of the ulcer margin in 56.5% of the ulcers, and 51-100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. CONCLUSION: Our data suggest that 'the red lipstick sign' could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing.

Cognitive and psychiatric signs revealing Sneddon syndrome: A case report.

Key Clinical Message: The diagnosis of Sneddon Syndrome should be considered in adults with young-onset dementia accompanied by neuropsychiatric signs and livedo racemosa. Magnetic resonance imaging and cerebral angiography are essential. A cutaneous biopsy may help in the diagnosis. Abstract: Sneddon syndrome (SS) is a clinical entity corresponding to a noninflammatory thrombotic vasculopathy that typically includes livedo racemosa and cerebrovascular ischemia. Psychiatric symptoms with cognitive impairment often occur but are rarely the inaugural symptoms. We present a case of secondary SS in a 45-year-old man in whom dementia and psychosis revealed the disease.

Deficiency of adenosine deaminase 2 as an unrecognized cause of early-onset stroke and cranial nerve palsy.

OBJECTIVE: The aim of this study is to evaluate the clinical, laboratory, and radiological findings and prognosis of patients with adenosine deaminase 2 deficiency (DADA2) and to highlight the conditions that DADA2 should be considered in the differential diagnosis in patients with neurological findings. METHODS: A case series of six DADA2 patients was presented in this retrospective, descriptive study. Clinical and laboratory data, treatment protocols, and prognosis of the patients were recorded. A diagnosis of DADA2 was established by ADA2 enzyme activity assay and/or ADA2 gene sequencing. RESULTS: Six patients with DADA2 were included in the study. The median age at symptom onset was 6.5 years (range 3.5-13.5 years). The median time to diagnosis from the initial presentation was 9 (3-72) months. Consanguinity was present in the families of 4 cases. The skin, nervous system, and musculoskeletal system were the most commonly involved systems. Vasculitis mimicking polyarteritis nodosa (PAN) was the predominant phenotype (n=4) in our case series. Four patients with PAN-like features had neurological involvement. Ischemic strokes were found in 3 patients, cranial nerve palsy in 2 patients, and seizures in 2 patients. The CECR1 gene was analyzed in all patients. We analyzed plasma ADA2 enzyme activity only in one patient. Anti-tumor necrosis factor (TNF)-α therapy was initiated. Inflammation was suppressed and remission was achieved in all patients. CONCLUSION: DADA2 should be considered in patients with PAN-like disease, a history of familial PAN/vasculitis, early-onset strokes/neurological involvement with systemic inflammation. Furthermore, anti-TNF-α therapy appears to be beneficial for the treatment of DADA2.

Livedo reticularis y dengue

Se presenta a un varón de 40 años, residente en la ciudad de Lima, sin viajes recientes, con fiebre, malestar general, cefalea y diarrea. Acudió al Servicio de Emergencia y los exámenes auxilares mostraron leucopenia y trombocitopenia leve. Los estudios para Epstein-Barr, hepatitis B, toxoplasma, rubéola, citomegalovirus, herpes 1 y 2 y COVID-19 fueron negativos. Los anticuerpos IgM y IgG para dengue fueron negativos, y la proteína NS1 fue positiva. El paciente fue diagnosticado con dengue y solo recibió paracetamol. En el seguimiento, en el séptimo día de enfermedad, se le halló afebril y con lesiones dérmicas tipo livedo reticularis en los miembros, principalmente. Se resalta este inusual patrón cutáneo en dengue.

We present the case of a 40-year-old male, resident of Lima city, with no recent travels, with fever, general malaise, headache and diarrhea. He went to the Emergency Department and auxiliary tests showed leukopenia and mild thrombocytopenia. Studies for Epstein-Barr, hepatitis B, toxoplasma, rubella, CMV, herpes 1-2 and COVID-19 were negative. IgM and IgG antibodies for dengue were negative and NS1 protein was positive. He was diagnosed with dengue. He only received paracetamol. On follow-up, on the seventh day of illness, he was found afebrile and with livedo reticularis type dermal lesions on the limbs, mainly. This unusual cutaneous pattern in dengue is highlighted.

Endothelial dysfunction, thrombophilia, and nailfold capillaroscopic features in livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers, livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease. OBJECTIVES: This study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology. METHODS: This case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients. RESULTS: Plasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05-2.79] ng/ml vs. 1.89 [1.43-2.33] ng/ml, p = 0.007; 1.15 [0.88-1.4] ng/ml vs. 0.76 [0.56-0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26-18.26] vs. 19.80 % [16.47-24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-ß2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %). CONCLUSIONS: In conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways.

An Eight-Year-Old Child With Sneddon Syndrome: A Rare Case Report.

We present a rare case of slow-progressing neurocutaneous vasculopathy described as Sneddon syndrome. A child presented with global developmental delay, congenital livedo racemosa, unilateral vision loss, and a past history of focal neurological deficit. Our main objective is to make physicians aware of this nature of presentation in children.